TGF beta receptor 2

Transforming growth factor, beta receptor II (70/80kDa)
PDB rendering based on 1ktz.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1KTZ​, 1M9Z​, 1PLO​, 2PJY​, 3KFD​
Identifiers
Symbols	TGFBR2 ; AAT3; FAA3; LDS1B; LDS2; LDS2B; MFS2; RIIC; TAAD2; TGFR-2; TGFbeta-RII
External IDs	OMIM: 190182 MGI: 98729 HomoloGene: 2435 ChEMBL: 4267 GeneCards: TGFBR2 Gene
EC number	2.7.11.30
Gene ontology Molecular function • transmembrane receptor protein serine/threonine kinase activity • receptor signaling protein serine/threonine kinase activity • transforming growth factor beta-activated receptor activity • transforming growth factor beta receptor activity, type II • protein binding • ATP binding • glycosaminoglycan binding • mitogen-activated protein kinase kinase kinase binding • type I transforming growth factor beta receptor binding • type III transforming growth factor beta receptor binding • SMAD binding • metal ion binding • transforming growth factor beta binding Cellular component • cytosol • plasma membrane • caveola • external side of plasma membrane • integral component of membrane • receptor complex • transforming growth factor beta receptor homodimeric complex Biological process • blood vessel development • patterning of blood vessels • vasculogenesis • in utero embryonic development • positive regulation of mesenchymal cell proliferation • lens development in camera-type eye • positive regulation of tolerance induction to self antigen • positive regulation of B cell tolerance induction • positive regulation of T cell tolerance induction • growth plate cartilage chondrocyte growth • protein phosphorylation • receptor-mediated endocytosis • apoptotic process • transforming growth factor beta receptor signaling pathway • common-partner SMAD protein phosphorylation • smoothened signaling pathway • gastrulation • brain development • heart development • embryo implantation • aging • response to nutrient • positive regulation of cell proliferation • response to mechanical stimulus • response to glucose • regulation of gene expression • positive regulation of epithelial cell migration • peptidyl-serine phosphorylation • peptidyl-threonine phosphorylation • signal transduction by protein phosphorylation • negative regulation of transforming growth factor beta receptor signaling pathway • organ regeneration • activation of protein kinase activity • embryonic hemopoiesis • wound healing • regulation of cell proliferation • response to drug • myeloid dendritic cell differentiation • positive regulation of skeletal muscle tissue regeneration • response to estrogen • positive regulation of angiogenesis • digestive tract development • positive regulation of smooth muscle cell proliferation • embryonic cranial skeleton morphogenesis • positive regulation of NK T cell differentiation • palate development • negative regulation of cardiac muscle cell proliferation • pathway-restricted SMAD protein phosphorylation • bronchus morphogenesis • trachea formation • mammary gland morphogenesis • lung lobe morphogenesis • response to cholesterol • lens fiber cell apoptotic process • positive regulation of reactive oxygen species metabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7048	21813
Ensembl	ENSG00000163513	ENSMUSG00000032440
UniProt	P37173	Q62312
RefSeq (mRNA)	NM_001024847	NM_009371
RefSeq (protein)	NP_001020018	NP_033397
Location (UCSC)	Chr 3: 30.61 – 30.69 Mb	Chr 9: 116.09 – 116.18 Mb
PubMed search

Transforming growth factor, beta receptor II (70/80kDa) is a TGF beta receptor. TGFBR2 is its human gene.

It is a tumor suppressor gene.^[1]

Function

This gene encodes a member of the serine/threonine protein kinase family and the TGFB receptor subfamily. The encoded protein is a transmembrane protein that has a protein kinase domain, forms a heterodimeric complex with another receptor protein, and binds TGF-beta. This receptor/ligand complex phosphorylates proteins, which then enter the nucleus and regulate the transcription of a subset of genes related to cell proliferation. Mutations in this gene have been associated with Marfan syndrome, Loeys-Deitz aortic aneurysm syndrome, Osler-Weber-Rendu syndrome, and the development of various types of tumors. Alternatively spliced transcript variants encoding different isoforms have been characterized.^[2]

Interactions

TGF beta receptor 2 has been shown to interact with:

• AP2B1,^[3]
• Cyclin B2,^[4]
• Endoglin,^[5][6]
• Heat shock protein 90kDa alpha (cytosolic), member A1^[7]
• STRAP,^[8][9]
• TGF beta receptor 1,^[10][11] and
• Transforming growth factor, beta 3.^{[5][12][13][14]}

Domain architecture

Transforming growth factor beta receptor 2 ectodomain
crystal structure of human tgf-beta type ii receptor ligand binding domain
Identifiers
Symbol	ecTbetaR2
Pfam	PF08917
InterPro	IPR015013
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

TGF beta receptor 2 consists of a C-terminal protein kinase domain and an N-terminal ectodomain. The ectodomain consists of a compact fold containing nine beta-strands and a single helix stabilised by a network of six intra strand disulphide bonds. The folding topology includes a central five-stranded antiparallel beta-sheet, eight-residues long at its centre, covered by a second layer consisting of two segments of two-stranded antiparallel beta-sheets (beta1-beta4, beta3-beta9).^[13]

See also

• TGF beta receptors

References

1. "TGFBR2 - transforming growth factor, beta receptor II (70/80kDa) - Genetics Home Reference". Retrieved 2008-09-07.
2. "Entrez Gene: TGFBR2 transforming growth factor, beta receptor II (70/80kDa)".
3. Yao D, Ehrlich M, Henis YI, Leof EB (Nov 2002). "Transforming growth factor-beta receptors interact with AP2 by direct binding to beta2 subunit". Molecular Biology of the Cell 13 (11): 4001–12. doi:10.1091/mbc.02-07-0104. PMC 133610. PMID 12429842.
4. Liu JH, Wei S, Burnette PK, Gamero AM, Hutton M, Djeu JY (Jan 1999). "Functional association of TGF-beta receptor II with cyclin B". Oncogene 18 (1): 269–75. doi:10.1038/sj.onc.1202263. PMID 9926943.
5. Barbara NP, Wrana JL, Letarte M (Jan 1999). "Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily". The Journal of Biological Chemistry 274 (2): 584–94. doi:10.1074/jbc.274.2.584. PMID 9872992.
6. Guerrero-Esteo M, Sanchez-Elsner T, Letamendia A, Bernabeu C (Aug 2002). "Extracellular and cytoplasmic domains of endoglin interact with the transforming growth factor-beta receptors I and II". The Journal of Biological Chemistry 277 (32): 29197–209. doi:10.1074/jbc.M111991200. PMID 12015308.
7. Wrighton KH, Lin X, Feng XH (Jul 2008). "Critical regulation of TGFbeta signaling by Hsp90". Proceedings of the National Academy of Sciences of the United States of America 105 (27): 9244–9. doi:10.1073/pnas.0800163105. PMC 2453700. PMID 18591668.
8. Datta PK, Chytil A, Gorska AE, Moses HL (Dec 1998). "Identification of STRAP, a novel WD domain protein in transforming growth factor-beta signaling". The Journal of Biological Chemistry 273 (52): 34671–4. doi:10.1074/jbc.273.52.34671. PMID 9856985.
9. Datta PK, Moses HL (May 2000). "STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling". Molecular and Cellular Biology 20 (9): 3157–67. doi:10.1128/mcb.20.9.3157-3167.2000. PMC 85610. PMID 10757800.
10. Kawabata M, Chytil A, Moses HL (Mar 1995). "Cloning of a novel type II serine/threonine kinase receptor through interaction with the type I transforming growth factor-beta receptor". The Journal of Biological Chemistry 270 (10): 5625–30. doi:10.1074/jbc.270.10.5625. PMID 7890683.
11. Razani B, Zhang XL, Bitzer M, von Gersdorff G, Böttinger EP, Lisanti MP (Mar 2001). "Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor". The Journal of Biological Chemistry 276 (9): 6727–38. doi:10.1074/jbc.M008340200. PMID 11102446.
12. De Crescenzo G, Pham PL, Durocher Y, O'Connor-McCourt MD (May 2003). "Transforming growth factor-beta (TGF-beta) binding to the extracellular domain of the type II TGF-beta receptor: receptor capture on a biosensor surface using a new coiled-coil capture system demonstrates that avidity contributes significantly to high affinity binding". Journal of Molecular Biology 328 (5): 1173–83. doi:10.1016/s0022-2836(03)00360-7. PMID 12729750.
13. Hart PJ, Deep S, Taylor AB, Shu Z, Hinck CS, Hinck AP (Mar 2002). "Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex". Nature Structural Biology 9 (3): 203–8. doi:10.1038/nsb766. PMID 11850637.
14. Rotzer D, Roth M, Lutz M, Lindemann D, Sebald W, Knaus P (Feb 2001). "Type III TGF-beta receptor-independent signalling of TGF-beta2 via TbetaRII-B, an alternatively spliced TGF-beta type II receptor". The EMBO Journal 20 (3): 480–90. doi:10.1093/emboj/20.3.480. PMC 133482. PMID 11157754.

External links

• GeneReviews/NIH/NCBI/UW entry on Thoracic Aortic Aneurysms and Aortic Dissections

This article incorporates text from the public domain Pfam and InterPro IPR015013